Study of a Neuroprotective Drug to Limit the Extent of Damage From an Ischemic Stroke (MINOS)

This study has been completed.
Sponsor:
Collaborators:
University of Kentucky
Oregon Health and Science University
Information provided by (Responsible Party):
David Hess, MD, Georgia Health Sciences University
ClinicalTrials.gov Identifier:
NCT00630396
First received: February 28, 2008
Last updated: December 9, 2011
Last verified: December 2011

February 28, 2008
December 9, 2011
May 2008
January 2010   (final data collection date for primary outcome measure)
Maximally Tolerated Dose of IV Minocycline [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
Investigators closely monitored each subject for evidence of minocycline intolerance. All adverse events were immediately reported for a decision whether to discontinue the study medication and/or reduce the dose. A computer program was used to determine the maximum tolerated dose. After entering information regarding doses and expected toxicities, results for each subject as they were collected were entered. The computer program informed as to (de)escalation, or maintenance of the same dose in the subsequent cohort of enrolled patients.
The objective of this project is to determine the maximally tolerated intravenous dose of minocycline in ischemic stroke patients. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00630396 on ClinicalTrials.gov Archive Site
  • Half-life of IV Minocycline [ Time Frame: For each subject blood samples were drawn before dose #1 and one hour after starting dose #1. Additional blood was drawn 1, 6, 12, 24, 48, and 72 hours after starting dose #6, which lasted approximately 6 days. ] [ Designated as safety issue: No ]
    In eligible patients enrolled at Georgia Health Sciences University, blood samples were drawn for quantification of minocycline serum concentrations. This enabled the study team to determine the half life of the study drug.
  • 90 Day Modified Rankin Scale Score [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    The modified Rankin Scale (mRS) was performed in person at the 90 day clinic follow-up appointment. The modified Rankin Scale is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke. The scale runs from 0-6. 0 represents no symptoms. 1 represents no significant disability. 2 represents slight disability. 3 represents moderate disability. 4 represents moderately severe disability. 5 represents severe disability. 6 represents death.
  • Determine the pharmacokinetics of Minocycline in patients with ischemic stroke [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Determine the effect of the different doses of MC on plasma MMP-9 activity. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Gather preliminary data of the effect of different doses of MC on functional outcome [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study of a Neuroprotective Drug to Limit the Extent of Damage From an Ischemic Stroke
Minocycline to Improve Neurologic Outcome in Stroke (MINOS)

The primary aim of this study is to find out which of 4 different doses of minocycline are safe and well tolerated so that we will know the optimal dose to test in future patients.

Minocycline is a widely used antibiotic and is approved by the Food and Drug Administration (FDA) for treatment of infections and acne. However, doctors do not know whether minocycline will work in stroke patients. Its use in stroke patients is experimental. There is a lot of information from experimental stroke studies in animals that minocycline lessens the damage from a stroke and the animals recover better. Since minocycline is generally a very safe drug in humans and does not have a lot of side effects, investigators at Georgia Health Sciences University (formerly the Medical College of Georgia) believe that it might be a safe and effective drug to improve the outcome in patients with stroke.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Stroke, Acute
Drug: Minocycline

Dose level 1 = 3mg/kg intravenous (IV) initial dose, followed by 1.5mg/kg every 12 hours times 5 more doses.

Dose level 2 = 4.5mg/kg intravenous (IV) initial dose, followed by 2.25mg/kg every 12 hours times 5 more doses.

Dose level 3 = 6 mg/kg intravenous (IV) initial dose, followed by 3 mg/kg every 12 hours times 5 more doses.

Dose level 4 = 10 mg/kg intravenous (IV) initial dose, followed by 5 mg/kg every 12 hours times 5 more doses

Other Names:
  • Minomycin
  • Minocycline hydrochloride
  • Minocycline hydrochloride injection
  • Minomycin Intravenous (for drip use)
  • Minomycin Intravenous
  • MINO
Not Provided
Fagan SC, Waller JL, Nichols FT, Edwards DJ, Pettigrew LC, Clark WM, Hall CE, Switzer JA, Ergul A, Hess DC. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. Stroke. 2010 Oct;41(10):2283-7. Epub 2010 Aug 12.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
January 2010
January 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • over 18 years of age
  • acute onset focal neurologic deficit consistent with acute ischemic stroke, or computed tomographic scan consistent with acute cerebral ischemia
  • onset of symptoms less than 6 hours
  • measurable neurologic deficit (National Institutes of Health [NIH] Stroke Scale >/= 1)

Exclusion Criteria:

  • allergy to tetracycline antibiotics
  • women of child-bearing potential
  • known hepatic and/or renal insufficiency
  • Thrombocytopenia
  • history of intolerance to minocycline
  • dizziness at the time of stroke or in the past month (by self-report)
  • aphasia likely to interfere with patients ability to report adverse effects
  • previous functional disability
  • stuporous or comatose
  • presence of another serious illness likely to confound the study
  • unlikely to be available for 90 day follow-up
  • severe stroke (National Institutes of Health [NIH] Stroke Scale >22)
  • undergoing an interventional neuro-radiological intervention in first 12 hour
Both
19 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00630396
RO1 NS055728-01A1, 07-02-202
Yes
David Hess, MD, Georgia Health Sciences University
David Hess, MD
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • University of Kentucky
  • Oregon Health and Science University
Principal Investigator: David C Hess, MD Georgia Regents University
Georgia Regents University
December 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP